Bis-quaternary salts of 1:10-bis-(dialkylamino)-5:6-dithia-decane



UNITED srnrs Patented Aug. 11, 1953 PATENT BIS-QUATERNARY SALTS OF 1:10-BIS-(DI- ALKYLAMINO) -5 :6-DITHIA-DECANE No Drawing. Application September 19, 1951,

OFFECE Serial No. 247,383. In Great Britain September 2 Claims. (Cl. 260-567.6)

The present invention is concerned with im: provements in' cr relating to bis-(aminoalkyD- disulphides, more particularly bis-(dimethylor diethyl-aminoalkyl)-disulphides wherein the alkyl group is a butyl; amyl, hexyl or heptyl group, and quaternary salts thereof.

Bis-dimethylaminoethyland bis-dimethylaminopropyl-disulphides in the form of their dimethiodides are already known [see J. A. C. S., 1938, 60, 1765]. The preparation of bis-diethylaminoethyl-disulphide and bisdiethylaminoprop-yl-disulphide has also been disclosed [see J. A. C. S. 1945, 67, 1845 et seq.]. The free bases were produced by treating the diethylaminoethylthiol or diethylaminopropyl-thiol, in the form of its sodium salt, with iodine.

It has now been found, according to the present invention, that quaternary salts of bis-(dimethyland diethylaminoalkyl) disulphides having from 4-. to 7 carbon atoms in the alkyl groups thereof hale a particular high Hare-like understood by reference to the following formulaactivity when compared with similar compounds having a lesser number of carbon atoms in the 2 roup, and Z represents an alkali metal, hydrogen or the radical NHFX X being a halogen atom, or a hydrohalide or alkyl halide thereof, and, as the case may be, reacting the disulphide of the general formula formed with an alkyl halide or a dialkyl sulphate to produce the corresponding quaternary nitrogen base.

The various modes of formation of the compounds of the present invention can be better scheme which is given byway of illustration:

alkyl groups thereof. j: NHnX- 7 R1 Accordingly the present invention comprises 2 bis-(dimethyland diethyl-aminoalkyl) -disu1 P i r811 phides wherein the alkyl group is a butyl, amyl, R1 p N112 R hexyl 'or a heptyl group and quaternary salts 1 t thereof. [H+X] E The compound of the present invention can OH be represented by the following general formula: lMtOH 4 N-C4 7S N-C4 7S Mt N '}4 7 S R: 2 and R7 R2 Alk Rz7NC4 7S X= Halide R3 1 R1\ 7 I R1 wherein R1 and R2 are methyl or ethyl, R3 is an 40 R2N+ o 1-S .Mt R N+-C ws alkyl group, preferably methyl or ethyl, C4 '1 R3 -3 v represents a butyl, amyl, hexyl or heptyl group I v a I and X= represents two halogen ions, preferably 2 iodine ions, or a divalent anion such as a sulphate l 7 ion, and are new substances. 45 H Mton Mt.OH The present invention further provides a proc- M ess for the manufacture of the aforesaid novel H compounds, which comprises oxidizing by means NHQ' X- R1 of iodine a compound of the general formula RPNFC4 R R V a I I NHz R3 No4. 1 z 2':- wherein R1, R2, R3. and -04 7- have the values wherein R1 and R2 stand for methyl or ethyl, C4 7 represents a butyl, amyl, hexyl or heptyl given hereinbefore, X- is a halogen atom and Mt.

5 se alkaltm bodiment of the present invention, for example,v is about equal to that of tubocurarine in the dog" as test animal; that is, about ten-times as great an activity as that of bis-(diethy-l'aminopropyl)- disulphide diethiodide which is a previously prepared member of this class of. substance. This striking enhancement of activitywas surprising in view of the homologous nature of the;series.

The following examples illustrate the manner in which the novel substancesof the presentinvention may be prepared:

EXAMPLE 1 Preparation of 1-dz'methylamino-hutane--- filial-(4) Succinic anhydride (60 g.) was added slowly to 27% ethanolic dimethylamine (102 g.) cooled in ice. The mixture was left at C. for 12 hours and then cooled to 0 C. for 1 hour. The N,N- dimethyl-succinamic acid which separated was filtered off and recrystallized from benzene. It melted at 8485 C. Yield: 54% (46.6 g.).

N,N-dimethyl-succinamic acid (34.9 g.) was extracted from a Soxhlet into a stirred solution of lithium aluminium hydride (21 g.) in dry, boiling ether (1200 ml.) in a nitrogen atmosphere over the period of 24 hours. The complex formed was decomposed while in ether solution with ice-cold water and acidified 50% sulphuric acid. After washing with ether the acid solution was made strongly alkaline with 30% sodium hydroxyde and continuously extracted with ether for 24 hours. The ethereal solution was dried over anhydrous sodium. carbonate, the ether distilled off and the residue consisting of 4-dimethylamino-butane-olr(1), distilled at 14 mm. pressure when its boiling'point was 80-81 C. Yield: 49% (13.8.).

4-dimethylamino-butane-ol-(1) (13.1 g.) was dissolved in benzene (40 ml.) and the solution added slowly to thionyl chloride (16 ml.) in benzene (40 ml.). The mixture was then heated for 3 hours under reflux on' the water-bath. The benzene was then distilled off under reduced pressure and the residue recrystallized by'dissolving in ethanol and adding ether. A further recrystallization gave the required 4-dimethylaminobutylchloride hydrochloride; melting point 1l2-115 C. (very hygroscopic). Yield: 65% (12.5 g.).

4-dimethylaminobutyl-chloride hydrochloride (12.5 g.) was dissolved in ethanol (20 ml.). Thiourea (5.5 g.) was added and the solution was refluxed for 15 hours. Addition of ethyl acetate precipitated the 4-dimethylaminobutylisothiouronium chloride hydrochloride as a viscous syrup which was recrystallized by dissolving in ethanol, adding ethyl acetateuntil turbid and then scratching the walls of the flask; melting point 180183 C. (hygroscopic). Yield 63% (11.4 g.).

4 dimethylaminobutyl isothiouroniumchloride (11.4 g.) was dissolved in water (15 m1.) and 5 N caustic soda solution (18.4 ml.) was added. The mixture was heated at about 90 C. for 1 hour on a water-bath, then cooled in ice and extracted with ether. Afterdryingthe ethereal solution over anhydrous sodium sulphate the 4 ether was evaporated and the l-dimethylaminobutane-thiol-(4) formed distilled; boiling point 84 C. at 35 mm. Yield: 64% (3.9 g.).

EXAMPLE 2 Bis-(fi-trimethylammonium-butyl) disulphide diiodide 1-dimethylamino-butane-thiol-(4) (0.5 g.) was dissolved in 5 N caustic soda solution (0.7 cc.) and iodine, dissolved in potassium iodide solution, was added until a faint yellow color appeared. The excess of iodine was removed with a few drops of sodium. sulphite solution and the resulting; colorless solution was made definitely alkaline with dilute sodium hydroxide solution. An oilseparated which was extracted with ether. The ethereal extract wasdried over caustic soda and the ether was evaporated, finally in vacuo. A colorless oil (0.4 g.) remained. The methiodide was prepared by taking up the oil in dry benzene (5 cc.) and adding methyl iodide (0.4 cc.). A yellow oil separated which crystallized on standing. Recrystallization from alcohol gave colorless crystals (0.5 g.), melting point 184-186 C. A further recrystallization slightly raised the melting point to 188-189 C. (uncorrected).

EXAMPLE .3

the ether was evaporated. The residual oil was,

distilled and 1:10 bis-(dimethylamino) -5:6- dithiadecane was collected, boiling point 130 C'./0.2 mm. Yield: 70% (4.65 g).

The required methiooiide was prepared by dropping methyl iodide (3.2 cc.) dissolved in dry benzene (20 cc.) into a solution of the 1:10- bis- (dimethylamino) -5 G-dithiadecane (4.65 g.) in dry benzene (40 cc.) contained in a flask fitted with a reflux condenser. During the addition the flask was shaken and cooled. The quaternary salt separated and the reaction mixture was allowed to stand for 15 hours. The slightly yellow product was collected by filtration, washed with ether, dried and recrystallized from ethanol, with two small crystals of sodium sulphite to decolorize the solution. Colorless crystals (9.1 g.) of the product were obtained, M. P. 194-195 C. A further recrystallization raised the melting point to l-l96 C.

This application is a GOIlbil'lllEtfiiOll ilT-Dlfi'. of our copending application Serial No. 243,582, filed August 24, 1951, now abandoned.

We claim: 1. A compound having the formula R1 R1 R2-NCH:CHzCH2CH2-S SCH2CH2CH2CH2-NRz x I R:

wherein R1, R2 and R3 each represents an alkyl radical having not more than two carbon atoms, and X represents an anion.

5 6 2. A compound having the formula OTHER REFERENCES CH3 /CHa Snyder et a1.: (I) J. Am. Chem. 800., vol. 69 CHs NCHzOHzCH20HrSSCHzCH2CHzCH2NCHa (1947) 2672-2674- Snyder et 211.: (II) J. Am. Chem. 800., vol. 70 5 (1948), pp. 2325 and 2826.

I I Renshaw et a1.: J. Am. Chem. 800., vol. 60

Gilman et aL: J. Am. Chem. $00., v01. 67

(1945), 1845 and 1846.

ALEXANDER LANG MORRISON. KENNETH JOHN MAYNARD ANDREWS.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,363,607 Mathes et a1. Nov. 28, 1944 2,401,234 Farlow May 28, 1946 

1. A COMPOUND HAVING THE FORMULA 